公开(公告)号：US09194862B2

公开(公告)日：2015-11-24

申请号：US12821738

申请日：2010-06-23

申请人： Catriona H. Jamieson ,  Annelie Schairer ,  Ifat Geron ,  Kim-Hien Dao ,  Daniel Jacob Goff

发明人： Catriona H. Jamieson ,  Annelie Schairer ,  Ifat Geron ,  Kim-Hien Dao ,  Daniel Jacob Goff

IPC分类号： C12Q1/00 ,  C12Q1/02 ,  G01N33/50 ,  C12Q1/68

CPC分类号： G01N33/5011 ,  C12Q1/6883 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N33/5073 ,  G01N2800/50

摘要： In alternative embodiments, the invention provides compositions and methods for determining the self-renewal potential of a cancer stem cell (CSC) through analysis of the cross-talk between cell self-renewal pathways leading to deregulation and enhanced self-renewal of the CSC, or for predicting the drugability (susceptibility to a drug) of a CSC, and/or for predicting the progression of a cancer that corresponds to the CSC, the method comprising detecting and quantifying in CSCs one or more B-cell lymphoma-2 (Bcl-2) family protein isoform(s) or transcripts (mRNAs, messages) encoding one or more Bcl-2 family protein(s) or protein isoform(s) thereof. In alternative embodiments, the invention provides compositions and methods to determine and measure the levels of Wnt, glycogen synthase kinase-3 beta (GSK-3 beta), glycogen synthase kinase-3 alpha (GSK-3 alpha), and/or Sonic Hedgehog Homolog (SHH or Shh) family proteins and alternatively spliced transcripts (mRNAs), and Wnt, GSK3beta, GSK3alpha and/or Shh family protein and alternatively spliced transcript ratios in cancer cells, e.g., stem cells, e.g., CSCs, for diagnostic, drug discovery and prognostic purposes.

摘要翻译： 在替代实施方案中，本发明提供了通过分析导致CSC的去调节和增强的自我更新的细胞自我更新途径之间的串扰来确定癌症干细胞（CSC）的自我更新潜力的组合物和方法， 或用于预测CSC的药物性（对药物的易感性）和/或用于预测与CSC相对应的癌症进展，所述方法包括在CSC中检测和定量一个或多个B细胞淋巴瘤-2（Bcl -2）家族蛋白质同种型或编码一种或多种Bcl-2家族蛋白或其蛋白质同种型的转录物（mRNA，消息）。 在替代实施方案中，本发明提供了确定和测量Wnt，糖原合酶激酶-3β（GSK-3β），糖原合酶激酶-3α（GSK-3α）和/或Sonic Hedgehog的水平的组合物和方法 同源物（SHH或Shh）家族蛋白和可变剪接的转录物（mRNA）和Wnt，GSK3beta，GSK3alpha和/或Shh家族蛋白，以及在癌细胞（例如，干细胞例如CSCs）中的剪接转录物比例用于诊断，药物 发现和预后目的。

公开(公告)号：US20110243853A1

公开(公告)日：2011-10-06

申请号：US12446203

申请日：2007-10-24

申请人： Catriona Helen M. Jamieson ,  Ken Kaushansky ,  Charlene Barroga ,  Ifat Geron ,  Annelie Schairer ,  Edward Kavalerchik

发明人： Catriona Helen M. Jamieson ,  Ken Kaushansky ,  Charlene Barroga ,  Ifat Geron ,  Annelie Schairer ,  Edward Kavalerchik

IPC分类号： A01K67/033 ,  A61K49/00 ,  C12Q1/02

CPC分类号： A01K67/0271 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2227/105 ,  A01K2267/0381 ,  C12N9/1205 ,  G01N33/5088

摘要： Non human animal models are provided for diseases involving erythroid function, particularly myeloproliferative disease. The models are useful for testing and screening of biologically active agents that affect erythropoiesis, and erythroid function. In the animal models of the invention, a hematopoietic stem or progenitor cell (HSC) population that has been genetically altered by the introduction of a mutant JAK2 coding sequence is transplanted into an immunocompromised, xenogeneic, non-human recipient. The recipient animal is engrafted with the cell population at a high frequency, and develops a myeloproliferative disorder characterized by polycythemia.

摘要翻译： 非人类动物模型适用于涉及红系功能的疾病，特别是骨髓增生性疾病。 该模型对于影响红细胞生成和红细胞功能的生物活性剂的测试和筛选是有用的。 在本发明的动物模型中，通过引入突变体JAK2编码序列遗传改变的造血干细胞或祖细胞（HSC）群体被移植到免疫受损的异种非人受体中。 受体动物以高频率移植细胞群，并发展出以红细胞增多症为特征的骨髓增生性疾病。